Valsartan is an angiotensin II antagonist and is known to be effective in the treatment of congestive heart failure and reducing blood pressure irrespective of age, sex or race and is also well tolerated. It has also been approved to treat people after heart attacks.
U.S. Pat. No. 5,399,578 describes the preparation of valsartan and its pharmaceutically acceptable salt.
U.S. Pat. Nos. 4,879,303 and 4,572,909 describes the preparation of amlodipine and its pharmaceutically acceptable salt. The compound amlodipine (3-ethyl 5-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methylpyridine-3,5-dicarboxylate) is a potent and long acting calcium channel blocker having utility as an anti-ischaemic and anti-hypertensive agent.
U.S. Pat. Nos. 6,294,197, 6,485,745 and 6,858,228 describe a solid oral dosage form of valsartan and optionally hydrochlorothiazide (HCTZ) prepared by compression method having more than 35% by weight based on total weight of the compressed solid oral dosage form, of the active ingredient.
U.S. Pat. No. 6,395,728 disclose combination of valsartan and amlodipine comprising from about 10 mg to about 200 mg of valsartan and 1 mg to about 180 mg amlodipine.
Combination of amlodipine and valsartan is marketed under the brand name EXFORGE® (amlodipine and valsartan) available in four different strengths: 5 mg/160 mg; 10 mg/160 mg; 5 mg/320 mg and 10 mg/320 mg. It is used for the treatment of hypertension.
WO 2007/022113 relates to monolayer and bilayer solid dosage forms of a combination of valsartan and amlodipine. This application discloses that for the 320 mg/5 mg fixed dose combination of valsartan and amlodipine it was not possible to get a bioequivalent product unless a bilayer tablet formulation was used.
As a person skilled in the art is aware, a bilayer tablet can exhibit certain disadvantages from many processing related limitations. Specialized machines are required for producing such tablets and the tablets are susceptible to bilayer separation. Moreover, the process of making bilayered tablets is less economical.
In light of this it was highly desirable to prepare a single layer composition of the combination product, which would also be bioequivalent to the bilayer tablet.
We have now surprisingly, found that it is possible to prepare a single layered pharmaceutical composition comprising amlodipine and valsartan or their pharmaceutically acceptable salts thereof, wherein the composition is bioequivalent to a tablet combination dosage form of amlodipine and valsartan marketed under the trade name of EXFORGE® (amlodipine and valsartan).